Method and device for the detection of at least one luminescent substance

ABSTRACT

Disclosed is a device for detecting at least one luminescent substance, comprising a radiation source for emitting excitation radiation to the at least one luminescent substance. The excitation radiation is provided with at least one excitation wavelength at which the luminescent substance is excited so as to emit luminescent radiation. At least one radiation receiver is provided, which detects the luminescent radiation and is configured regarding the spectral sensitivity thereof in such a way that said radiation receiver is insensitive to the radiation emitted by the radiation source. The luminescent substance is located inside a measuring chamber that is essentially impermeable to the luminescent radiation and comprises at least one wall area which is transparent to the excitation radiation emitted by the radiation source. The radiation source is placed outside the measuring chamber such that the excitation radiation emitted by the radiation source is coupled into the inside of the measuring chamber by penetrating said wall area.

This invention relates to a device for the detection of at least oneluminescent substance, with a radiation source for the emission ofexcitation radiation to the at least one luminescent substance, wherebythe excitation radiation has at least one excitation wavelength at whichthe luminescent substance is excited to emit luminescent radiation, andwith at least one radiation receiver which is insensitive to theexcitation radiation for the detection of the luminescent radiation,whereby the luminescent substance is located in the interior of ameasurement chamber which is essentially impermeable to the radiation towhich the radiation receivers are sensitive, and whereby the radiationsource is located outside the measurement chamber such that theexcitation radiation is injected through a wall area of the measurementthat faces the radiation source and is transparent for the excitationradiation though the measurement chamber into the interior of themeasurement chamber.

A similar device of the prior art is described in EP-A-0 640 828. It hasa measurement chamber which has a wall area that is formed by adichroitic mirror, behind which, outside the measurement chamber, aradiation source is located which emits an excitation radiation throughthe wall area at a wavelength of approximately 302 nm (UV) into themeasurement chamber. In the interior of the measurement chamber, aplurality of reaction vessels are provided, in which samples are locatedthat are marked with a luminescent substance. The luminescent substanceis excited by the excitation radiation to emit a luminescence radiation,the wavelength of which is different from that of the excitationradiation. The measurement chamber is impermeable for the luminescentradiation. For the detection of the luminescent radiation, a CCD camerais located in the measurement chamber at some distance from the samples.This device of the prior art has a relatively complicated construction.

A device of the prior art described in U.S. Pat. No. 4,868,103 has aflashlamp as the radiation source and a photomultiplier tube as theradiation receiver. Between the radiation source and a sample thatcontains a luminescent substance to be tested on one hand, and betweenthe sample and the radiation receiver on the other hand, there arerespective optical interference filters. This device of the prior art istherefore correspondingly expensive.

U.S. Pat. No. 5,885,843 describes another device of the prior art with ameasurement chamber in which a photoluminescence aerogel is located. Asthe radiation source, outside the measurement chamber a UV lamp isprovided which emits UV radiation into the measurement chamber throughan optical filter. The UV radiation excites the photoluminescent aerogelto emit visible luminescent light which is detected with a photodiode.To prevent the light emitted by the radiation source from reaching thephotodiode, the optical filter is impermeable to the luminescent light.This device of the prior art also has a relatively complicatedconstruction.

The object of the invention is therefore to create a device of the typedescribed above which, with a simple and compact construction.

This invention teaches that the wall area is formed by a semiconductorsubstrate, and that the at least one radiation receiver is integrated inthe form of a semiconductor component into the semiconductor substrate.

The semiconductor substrate thereby advantageously performs a dualfunction, and in addition to acting as the support for the at least oneradiation receiver, also acts as a window for the injection of theexcitation radiation into the measurement chamber. The measurementchamber can then be manufactured particularly economically usingMicrosystems engineering methods. The device can thereby have verycompact dimensions. The measurement chamber shields, in the wavelengthrange that can be detected with the radiation receiver, the at least oneradiation receiver that is located in the measurement chamber or withinits external contour against scattered or spurious radiation that occursoutside the measurement chamber. Any spurious radiation that penetratesinto the wall of the measurement chamber is thereby either completelyextinguished or is at least so severely attenuated that after itpenetrates the wall it is practically no longer detected by theradiation receiver. Thus, in the wavelength range to be detected, themeasurement has a high level of protection against interference fromscattered or spurious radiation.

The device can optionally also be used as an optical coupler. In thatcase, the radiation source for the transmission of a signal can beconnected with a modulation device device [sic] and the radiationreceiver can be connected with a demodulation device. The term“luminescence” as used here means all emissions of radiation quanta,primarily luminous phenomena such as fluorescence or phosphorescence,that substances exhibit after quantum excitation.

In one advantageous configuration of the invention, the semiconductorsubstrate is a silicon substrate. Silicon is permeable for infraredlight at a wavelength of greater than approximately 1080 nm, which meansthat the radiation source for the excitation of the luminescentsubstance can be provided in the form of an infrared radiation source.The radiation receiver can be a silicon photodiode that is integratedinto the semiconductor substrate and is insensitive in this wavelengthrange.

In one particularly advantageous realization of the invention, thedevice is realized in the form of a thermal imaging camera which has aplurality of radiation receivers arranged in the measurement chamber,preferably in the form of a two-dimensional matrix, associated with atleast one of which receivers is an optical imaging system for theimaging of the radiation source on the radiation receiver. In this case,in the interior of the measurement chamber, there can be a layer ofluminescent substance that extends continuously over the radiationreceiver. It is also conceivable, however, that the layer of luminescentsubstance has interruptions between the radiation receivers. The layerof luminescent substance can optionally occupy all of the space betweenthe walls of the measurement chamber located one on either side of thelayer of luminescent substance, i.e. the walls form a laminated stackwith the layer of luminescent . . . substance. The optical imagingsystem is preferably located outside the measurement chamber, betweenthe measurement chamber and the radiation source.

In one preferred embodiment of the invention, the luminescent substanceis realized so that the wavelength of the luminescent radiation is lessthan the excitation wavelength. Upward-converting luminescent substancesof this type are described in the prior art, such as EP 0 723 146 A1,for example. Examples of upward-converting luminescent substances arethe BND pigment manufactured by Dyomics GmbH, Jena and IR-140. Incontrast to downward-converting luminescent substances,upward-converting luminescent substances acquire the energy necessaryfor the quantum emission not from a single quantum effect, but from aplurality of quantum effects. Upward-converting luminescent substancestherefore have, in comparison to downward-converting luminescentsubstances, a significantly greater Stokes shift, at which thewavelength of the excitation radiation can be, for example, twice asgreat as the wavelength of the luminescent radiation. Consequently it ispossible to provide, as the radiation source, an infrared semiconductorradiation source, in particular a semiconductor diode, which makes itpossible to have a high radiation intensity with compact dimensions. Theinfrared light from such semiconductor radiation sources also has theadvantage that fewer spurious effects occur than with short-wave opticalradiation. By means of the upward-converting luminescent substance, theoptical radiation emitted by the semiconductor radiation source can beconverted into visible light or into near-infrared light, so that aneconomical opto-electronic semiconductor sensor can be provided as theradiation receiver, which has a high detection sensitivity in thiswavelength range.

It is advantageous if a boundary wall of the measurement chamber that isopposite the wall area is realized in the form of a reflector for thereflection of the excitation radiation. The radiation injected into themeasurement chamber can then be used more efficiently for the excitationof the at least one luminescent substance.

In an additional advantageous realization of the invention, the wallarea is connected with the interior of the measurement chamber by meansof an optical waveguide, whereby the waveguide preferably runs parallelto the plane of extension of the wall area, in particular on its insidefacing the luminescent substance. The radiation provided for theexcitation of the luminescent substance is then conducted withparticularly low losses into the interior of the measurement chamber, sothat there is a uniform excitation of the luminescent substance alongthe semiconductor substrate. The excitation of the luminescentsubstance, which is preferably located on the totally reflectiveboundary surface of the waveguide or immediately adjacent to it, occursby means of the evanescence field of the radiation guided in thewaveguide. The radiation can be injected into the waveguide by means ofa prism and/or an optical lattice on which the radiation is deflected sothat it subjected to total reflection when it strikes a boundary surfaceof the waveguide.

In one advantageous realization of the invention, a measurement signaloutput of at least one radiation receiver is connected directly orindirectly by means of an analysis device with a transponder for thetransmission of the measurement signal or of a signal derived from it toa receiver part, whereby the transponder is preferably integrated intothe semiconductor substrate. The measurement signal measured by means ofat least one radiation receiver can then be transmitted wirelessly tothe receiver section and from there to an analysis section, to a displaydevice and/or a data storage component. In that case, the device isparticularly well suited for mobile use. Optionally it is also possibleto connect the measurement chamber with an object or to integrate it insaid object, to make it possible to verify the genuineness of theobject. In that case, the object can be a credit card, a bill orbanknote or an item of clothing (designer clothing), for example. Toverify the genuineness of the object, the measurement chamber located onit is irradiated with the excitation light and the measurement signalmeasured by means of the radiation receiver is compared with a referencesignal.

In one embodiment of the invention, in the interior of the measurementchamber there are at least two luminescent substances with excitationwavelengths that are different from each other, whereby associated witheach of these luminescent substances is a radiation source with aspectral distribution that is adapted to the excitation wavelength ofthe respective luminescent substance. The radiation sources can then beoptionally modulated and in particular turned on and off in alternation.By means of a comparison of the measurement signal of the radiationreceiver with the modulation signal, it can be determined whether theappropriate luminescent substance is or is not present in themeasurement chamber.

In one advantageous configuration of the invention, the measurementchamber is realized in the form of a flow-through measurement chamberwith an interior cavity, at least one inlet opening and at least oneoutlet opening. In the measurement chamber, biomolecules orbiocomponents, for example, can then be examined and supplied with anutrient fluid by means of the inlet and outlet opening. The biomoleculecan be, for example, nucleic acids or derivates thereof (DNA, RNA, PNA,LNA, oligonucleotides, plasmids, chromosomes), peptides, proteins(enzyme, protein, oligopeptide, cellular receptor proteins and complexesthereof, peptide hormones, antibodies and fragments thereof),carbohydrates and their peptide hormones, antibodies and fragmentsthereof), carbohydrates and derivatives thereof, in particularglycolized proteins and glycosides, fats, fatty acids and/or lipids.

In one preferred embodiment of the invention, in the interior cavity, atleast one receptor for a ligand, in particular for a biomolecule, abiological cell and/or at least one fragment thereof is immobilized onthe surface of at least one radiation receiver, whereby the ligand ismarked with the at least one luminescent substance. In this case, theterm “receptor” means a molecule that can be bonded to a surface and canenter into a bond with a second molecule, the ligand. Receptors include,for example, but are not limited to: nucleic acids and derivativesthereof (DNA, RNA, PNA, LNA, oligonucleotides, plasmids, chromosome),peptides and proteins (enzymes, proteins, oligopeptides, cellularreceptor proteins and complexes thereof, peptide hormones, antibodiesand fragments thereof), carbohydrates and byproducts thereof, inparticular glycolized proteins and glycosides. The receptor, however,can also include more complex structures such as cells and fragmentsthereof, for example. The term “ligands” as used here means moleculesthat can form a more or less specific bond with a receptor. Ligandsinclude, for example, but are not limited to: nucleic acids andderivatives thereof (DNA, RNA, PNA, LNA, oligonucleotides, plasmids,chromosomes), peptides and proteins (enzymes, proteins, oligopeptides,cellular receptor proteins and complexes thereof, peptide hormones,antibodies and fragments thereof, carbohydrates and derivatives thereof,in particular glycolized proteins and glycosides, gats, fatty acids andlipids, cells and fragments thereof, as well as all pharmacologicallyand toxicologically active substances. The receptor can be imprinted onthe radiation receiver, if necessary. A polyimide layer can be placedbetween the radiation receiver and the receiver to improve the adherenceof the receptor to the radiation receiver.

It is advantageous if there are a plurality of radiation receivers onthe semiconductor substrate, preferably in the form of a two-dimensionalarray, arranged next to one another, and if different receptors arelocated on the radiation receivers, if necessary. The device then makesit possible to examine analytes for the presence of a number ofdifferent ligands.

It is particularly advantageous if at least two of the differentreceptors have a different affinity for at least one ligand marked withthe luminescent substance, and if, optionally, there are more than tworeceptors that have a graduated affinity for the at least one ligand. Aradiation receiver on which a receptor with a high affinity for theligand is located then delivers a measurement signal even at a lowconcentration of the ligand in an analyte to be tested in themeasurement chamber. A radiation receiver on which a receptor with a lowaffinity to the ligand is located delivers a measurement signal only ata correspondingly higher concentration of the ligand if the measurementsignal from the first above named radiation receiver is already atsaturation. A device that has a corresponding number of receptors withgraduated affinity thus makes possible a determination of theconcentration of the ligands over a wide dynamic range. The devicethereby makes it possible to perform a measurement of the concentrationof the ligand with great accuracy both on ligands that are present in ahigh concentration and also on ligands that are present in a lowconcentration, without the requirement for the complex andtime-consuming dilution of the ligand. The receptors can be antibodiesthat are applied against various epitopes of the same ligand on theindividual radiation receivers but have different bonding constants. Itis also possible, however, for the affinity of at least one antibody tobe reduced by a chemical treatment.

The invention is explained in greater detail below, with reference tothe exemplary embodiments of the invention illustrated in theaccompanying drawings, several of which are only schematic:

FIG. 1 is a cross section through a flow-through measurement chamber, inthe interior cavity of which there is a luminescent substance, wherebythe flow-through measurement chamber has radiation receivers for themeasurement of the luminescent radiation,

FIG. 2 is a cross section through a device with a flow-throughmeasurement chamber that has a wall area that is permeable for anexcitation radiation and faces a reflective boundary wall, whereby theexcitation radiation is illustrated schematically in the form of beams,

FIG. 3 is a cross section through a flow-through measurement chamberthat has a wall area realized in the form of a waveguide, in which theexcitation radiation is guided,

FIG. 4 is a cross section through a radiation receiver on which areceptor layer is immobilized, which binds ligands marked by aluminescent substance,

FIG. 5 is an illustration similar to FIG. 4, whereby the luminescentsubstance is excited by means of excitation radiation for the emissionof luminescent radiation, whereby the excitation radiation and theluminescent radiation is illustrated schematically in the form of beams,

FIG. 6 is a partial cross section through a wall area of the measurementchamber which has a plurality of radiation receivers on which receptorsare immobilized, and

FIG. 7 is a graphical presentation of the spectral sensitivity of aphotodiode, whereby the wavelength in nanometers is plotted on theabscissa and the quantum efficiency in percent is plotted on theordinate.

A device designated 1 overall for the detection of at least oneluminescent substance 2 has a radiation source 3 which is shown onlyschematically in the drawing, and which is located and oriented so thatan excitation radiation 4 emitted by it strikes the luminescentsubstance 2. The radiation source 3 can be a semiconductor radiationsource, for example, in particular a light-emitting diode or a laserdiode. The spectrum of the excitation radiation 4 has at least oneexcitation wavelength at which the luminescent substance 2 is excited toemit luminescent radiation 5.

The luminescent substance 2 is located in the interior cavity 6 of ameasurement chamber 7, the walls of which are essentially impermeablefor the luminescent radiation 5. The measurement chamber 7 has a wallarea that faces the radiation source 3 and is permeable to theexcitation radiation 3 [sic-4?] and is formed by a disc-shaped orplate-shaped silicon semiconductor substrate 8. The semiconductorsubstrate 8 can be economically manufactured from a silicon wafer duringthe fabrication of the measurement chamber 7.

FIG. 2 shows that the radiation source 3 is located outside themeasurement chamber 7, and that the excitation radiation 4 is injectedthrough the semiconductor substrate 8 into the interior cavity 6 of themeasurement chamber 7. For the detection of the luminescent radiation 5emitted by the luminescent substance 2, a plurality of radiationreceivers 9 that are realized in the form of photo diodes are located onthe semiconductor substrate 8, and with their detection side face theinterior cavity 6 of the measurement chamber 7.

The spectral distribution of the excitation radiation 4 lies in awavelength range that is above approximately 1080 nm. As shown in FIG.7, the radiation receivers 9 are insensitive in this wavelength range.The luminescent substance 2 is an upward-converting luminescentsubstance 2 in which the wavelength of the luminescent radiation 5 isless than the wavelength of the excitation radiation 3. The energyrequired for the emission of a luminescent radiation quanta is therebyacquired from a plurality of radiation quanta of the radiation source 3.The spectrum of the luminescent radiation lies in a wavelength rangebelow 1080 nm, in which the radiation receivers 9 are sensitive. Theradiation receivers 9 therefore detect only the luminescent radiation 5and not the excitation radiation 4. The measurement chamber 7 isessentially impermeable for radiation that lies in the wavelength rangein which the radiation receivers 9 are sensitive. Thus the radiationreceivers 9 are shielded by the measurement chamber 7 againstinterference radiation 10 that occurs outside the measurement chamber 7.

FIGS. 1 to 3 show that the radiation receivers 9 are connected by meansof printed conductors with an actuator and analysis device 11 that isintegrated into the semiconductor substrate. The analysis device 11 hasan interface device, which is illustrated schematically in the drawing,for the connection with a higher-level display and/or analysis unit,such as a microcomputer, for example.

In the exemplary embodiment illustrated in FIG. 2, the boundary wall 12of the measurement chamber 7 that faces the semiconductor substrate 8 isrealized in the form of a reflector, on which the excitation radiation 4injected through the semiconductor substrate into the interior cavity 6of the measurement chamber 7 is reflected back into the interior cavity6. The excitation radiation 4 injected into the measurement chamber 7 isthereby conducted through the measurement chamber 7 a plurality of timesand can thus be utilized more efficiently for the excitation of theluminescent substance 2. The boundary wall 12 has a base body made ofsilicon which is provided with a coating that reflects the excitationradiation 4 on its inside facing the interior cavity 6.

In the exemplary embodiment illustrated in FIG. 3, the semiconductorsubstrate 8 is connected by means of an optical waveguide 13 with theinterior cavity of the measurement chamber 7. The excitation radiation4—starting from the radiation source to the interior cavity 6—firstpenetrates the semiconductor substrate 8 and then arrives at an opticalwindow of the waveguide 13, at which the excitation radiation 4 isinjected into the waveguide 13. The optical window is provided on aprism-shaped injection element 14. The waveguide 13 is realized in theform of a waveguide stratum that runs approximately parallel to theplane of extension of the semiconductor substrate 8 and is located onthe inside of the semiconductor 8 that faces the interior cavity 6. Inthe exemplary embodiment illustrated in FIG. 3, the waveguide stratum 13extends without interruption over the radiation receivers 9. Otherembodiments are also conceivable, however, in which the waveguidestratum 13 can have interruptions or discontinuities in the vicinity ofthe radiation receivers 9. The luminescent substance is excited by meansof the evanescence field of the excitation radiation 4 guided in thewaveguide 13, which extends into the interior cavity 6.

FIGS. 1 to 3 also show that the measurement chamber 7 is realized in theform of a flow cell or flow-through measurement chamber with an inletopening 15 and an outlet opening 16. Detection reactions can beperformed in the measurement chamber 7.

FIG. 4 shows that in the interior cavity of the measurement chamber, areceptor 17 is immobilized on the radiation receiver 9, which receptorbonds to a specific ligand. The immobilization of the receptor 17 can beachieved by, for example, a silanization or by a polyimide layer locatedon the radiation receiver 9, to which layer the receptor 17 adheres. Thereceptor 17 can be imprinted on the radiation receiver 9 or on thepolyimide layer that is located on it. In the exemplary embodimentillustrated in FIG. 4, the receptor 17 is a first antibody against adetermined epitope 18 of the ligand. After the bonding of the epitope 18to the receptor 17, the resulting antibody complex formed by the epitope18 and the receptor 19 is marked by means of a second antibody 19 thatbonds to the epitope 18. This antibody 19 is marked directly orindirectly with the luminescent substance 2. The luminescent substance 2can be a fluorescing due, for example.

In the exemplary embodiment illustrated in FIG. 6, the semiconductorsubstrate 8 has a plurality of radiation receivers 9, 9′, 9″¹ locatednext to one another, on which different receptors 17, 17′, 17″ areimmobilized. The receptors are selected so that they have a different,graduated affinity for a determined ligand. The receptor 17 thereby hasa high affinity, the receptor 17′ an intermediate affinity and thereceptor 17″ a low affinity for the epitope 18 of the ligand.Accordingly, a greater number of ligands bond to the receptor 17 than tothe receptor 17′. In a corresponding manner, the number of ligands thatbond to the receptor 17′ is greater than the number of ligands that bondto the receptor 17″. Because the ligands are marked with the luminescentsubstance 2 and this luminescent substance is excited by means of theradiation source 3 to emit luminescent radiation, there is a greaterintensity of the luminescent radiation on the radiation receiver 9 thanon the radiation receiver 9′. In a corresponding manner, the intensityof the luminescent radiation on the radiation receiver 9′ is greaterthan on the radiation receiver 9″. It is therefore possible to determinethe concentration of the ligands from the measurement signals from theradiation receivers 9, 9′, 9″. Because of the graduated affinity of thedifferent receptors 17, 17′, 17″, the device 1 makes it possible todetermine the concentration of the ligands over a wide dynamic range.¹ Translator's Note: In the German text, the references 9, 9, 9 and 17,17, 17 are written as series of three identical numbers. From thespacing of the characters it is likely that they should be 9, 9′, 9″ and17, 17′, 17″, although there are no ′ or ″ characters in thedescription. In the claims, however, they are written 9, 9′, 9. Thetranslation assumes they should be 9, 9′, 9″ and 17, 17′, 17″throughout.

The device 1 for the detection of at least one luminescent substance 2therefore has a radiation source 3 for the emission of excitationradiation 4 on the at least one luminescent substance 2. The excitationradiation 4 has at least one excitation wavelength at which theluminescent substance 2 is excited to the emission of luminescentradiation 5. For the detection of the luminescent radiation 5, there isat least one radiation receiver 9, 9′, 9″, which is realized withreference to its spectral sensitivity so that it is insensitive to theexcitation radiation 4 emitted by the radiation source 3. Theluminescent substance 2 is in the interior of a measurement chamber 7which is essentially impermeable to the luminescent radiation 5, wherebythe measurement chamber 7 has at least one transparent wall area that istransparent for the excitation radiation 4 emitted by the radiationsource 3. The radiation source 3 is therefore located outside themeasurement chamber 7 such that the excitation radiation 4 emitted bythe radiation source 3 is injected through the wall area into theinterior of the measurement chamber 7.

1-14. (canceled)
 15. A device for the detection of at least oneluminescent substance, with a radiation source for the emission ofexcitation radiation on the at least one luminescent substance, wherebythe excitation radiation has at least one excitation wavelength at whichthe luminescent substance is excited to emit luminescent radiation, andwith at least one radiation receiver which is insensitive to theexcitation radiation, for the detection of the luminescent radiation,whereby the luminescent substance is located in the interior of ameasurement chamber which is essentially impermeable to the radiation towhich the radiation receivers are sensitive, and whereby the radiationsource is located outside the measurement chamber such that theexcitation radiation is injected through a wall area of the measurementchamber that faces the radiation source and is transparent for theexcitation radiation through the measurement chamber into the interiorof the measurement chamber, wherein the wall area is formed by asemiconductor substrate and that the at least one radiation receiver isintegrated in the form of a semiconductor assembly into thesemiconductor substrate.
 16. The device as claimed in claim 15, whereinthe luminescent substance is realized so that the wavelength of theluminescent radiation is less than the excitation wavelength.
 17. Thedevice as claimed in claim 15, wherein the semiconductor substrate is asilicon substrate.
 18. The device as claimed in claim 15, wherein it isrealized in the form of a thermal imaging camera that has a plurality ofradiation receivers located in the measurement chamber in the form of atwo-dimensional matrix, with at least one associated optical imagingsystem for the imaging of the radiation source on the radiationreceivers.
 19. The device as claimed in claim 15, wherein a boundarywall of the measurement chamber facing the wall area is realized in theform of a reflector for the reflection of the excitation radiation. 20.The device as claimed in claim 15, wherein the transparent wall area isconnected by means of an optical waveguide with the interior of themeasurement chamber, and that the waveguide runs preferably parallel tothe plane of extension of the transparent wall area, in particular toits inside facing the luminescent substance.
 21. The device as claimedin claim 15, wherein a measurement signal output of at least oneradiation receiver is connected with a transponder for the transmissionof the measurement signal or of a signal derived from it to a receiverpart, and that the transponder is preferably integrated into thesemiconductor substrate.
 22. The device as claimed in claim 15, whereinin the interior of the measurement chamber there are at least twoluminescent substances with excitation wavelengths that are differentfrom each other, and that associated with each of these luminescentsubstances there are radiation sources with a spectral distributionadapted to the excitation wavelength of the respective luminescentsubstance.
 23. The device as claimed in claim 15, wherein themeasurement chamber is realized in the form of a flow-throughmeasurement chamber with an interior cavity, at least one inlet openingand at least one outlet opening.
 24. The device as claimed in claim 15,wherein the interior cavity, on the surface of at least one radiationreceiver, at least one receptor for a ligand, in particular for abiomolecule, a biological cell and/or at least one fragment of such aligand, biomolecule or cell is immobilized, and that the ligand ismarked with the at least one luminescent substance.
 25. The device asclaimed in claim 17, wherein a plurality of radiation receivers arelocated next to one another, preferably in the form of a two-dimensionalarray, on the semiconductor substrate, and that different receptors areoptionally located on the radiation receivers.
 26. The device as claimedin claim 24, wherein at least two of the different receptors have adifferent affinity for at least one ligand marked with the luminescentsubstance, and that optionally more than two receptors are provided thathave a graduated affinity for the at least one ligand.